Division of Nephrology and Center for Immunity, Inflammation and Regenerative Medicine, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Kidney Int. 2010 May;77(9):771-80. doi: 10.1038/ki.2010.12. Epub 2010 Feb 17.
Reperfusion following ischemia is associated with acute kidney injury and inflammation. Using a mouse model, we exposed the kidney to a nonlethal period of ischemia, rendering it refractory to future ischemia-induced dysfunction. This ischemic preconditioning is partially mediated by Treg lymphocytes that suppress immune responses. We found that this maneuver significantly inhibited the accumulation of neutrophils and macrophages, tubular necrosis, and loss of kidney function caused by a subsequent ischemia/reperfusion injury 1 week later. The initial ischemia/reperfusion caused a significant increase in CD4(+)CD25(+)FoxP3(+) and CD4(+)CD25(+)IL-10(+) Treg cells within the kidney at 7 days of reperfusion. Treatment of preconditioned mice with a Treg cell-depleting antibody (PC61) reversed the effect of preconditioning on kidney neutrophil accumulation and partially inhibited the functional and histological protection of preconditioning. Adoptive transfer of Treg cells in naive mice, before ischemia/reperfusion, mimicked the protective and anti-inflammatory effects of ischemic preconditioning on the kidney. These studies highlight the role of Treg cells in ischemic preconditioning.
缺血后再灌注与急性肾损伤和炎症有关。我们使用小鼠模型，使肾脏经历一段非致死性的缺血期，使其对未来的缺血性功能障碍具有抗性。这种缺血预处理部分是由调节性 T 淋巴细胞介导的，它抑制免疫反应。我们发现，这一操作显著抑制了随后缺血/再灌注损伤 1 周后引起的中性粒细胞和巨噬细胞积聚、肾小管坏死和肾功能丧失。最初的缺血/再灌注在再灌注 7 天时导致肾脏中 CD4(+)CD25(+)FoxP3(+)和 CD4(+)CD25(+)IL-10(+)调节性 T 细胞显著增加。用调节性 T 细胞耗竭抗体（PC61）处理预处理小鼠，逆转了预处理对肾脏中性粒细胞积聚的影响，并部分抑制了预处理的功能和组织学保护作用。在缺血/再灌注之前，将调节性 T 细胞过继转移到幼稚小鼠中，模拟了缺血预处理对肾脏的保护和抗炎作用。这些研究强调了调节性 T 细胞在缺血预处理中的作用。
